1. Field of the Invention
The present invention relates generally to the fields of oncology, molecular biology, cell biology, and cancer. More particularly, it concerns cancer classification using molecular markers and cancer therapy.
2. Description of Related Art
Esophageal adenocarcinoma (EAC) is one of the most aggressive cancers in the world, characterized by high mortality and poor prognosis (Jemal et al., 2009). In the U.S., EAC has increased at a frequency of 5%-10% per year since the 1980s, making it the fastest growing malignancy (Jemal et al., 2009). Despite multidisciplinary therapeutic approaches, EAC remains a virulent disease with an overall 5-year survival rate<20% (Hongo et al., 2009). It is very urgent to discover novel therapeutic targets for prevention and establish biomarkers useful for early detection of high-risk populations. Esophageal chronic inflammation induced by gastro-esophageal reflux disease is an important factor contributing to EAC (Lambert and Hainaut, 2007a; Lambert and Hainaut, 2007b), and some inflammation-related cytokines have been found to play pivotal roles in the development of EAC, especially tumor necrosis factor (TNF) α (Eksteen et al., 2001).
Hedgehog signaling plays a role in many stages of development, especially in formation of left-right symmetry. Loss or reduction of hedgehog signaling leads to multiple developmental deficits and malformations, one of the most striking of which is cyclopia. Many cancers and proliferative conditions have been shown to depend on the hedgehog pathway. The growth of such cells and survival can be affected by treatment with the compounds disclosed herein.
The need still exists for identifying new cancer therapies, in particular new uses for hedgehog inhibitors, alone or in combination with other therapeutic agents, for treatment of cancer, especially esophageal cancers that are resistant to hedgehog modulation.